Gross R E, Mehler M F, Mabie P C, Zang Z, Santschi L, Kessler J A
Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Neuron. 1996 Oct;17(4):595-606. doi: 10.1016/s0896-6273(00)80193-2.
The epigenetic signals that regulate lineage development in the embryonic mammalian brain are poorly understood. Here we demonstrate that a specific subclass of the transforming growth factor beta superfamily, the bone morphogenetic proteins (BMPs), cause the selective, dose-dependent elaboration of the astroglial lineage from murine embryonic subventricular zone (SVZ) multipotent progenitor cells. The astroglial inductive effect is characterized by enhanced morphological complexity and expression of glial fibrillary acidic protein, with concurrent suppression of neuronal and oligodendroglial cell fates. SVZ progenitor cells express transcripts for the appropriate BMP-specific type I and II receptor subunits and selective BMP ligands, suggesting the presence of paracrine or autocrine developmental signaling pathways (or both). These observations suggest that the BMPs have a selective role in determining the cell fate of SVZ multipotent progenitor cells or their more developmentally restricted progeny.
调控哺乳动物胚胎大脑细胞谱系发育的表观遗传信号目前还知之甚少。在此我们证明,转化生长因子β超家族的一个特定亚类——骨形态发生蛋白(BMPs),可促使小鼠胚胎脑室下区(SVZ)多能祖细胞选择性地、剂量依赖性地分化为星形胶质细胞谱系。星形胶质细胞诱导效应的特征在于形态复杂性增强以及胶质纤维酸性蛋白的表达,同时抑制神经元和少突胶质细胞的细胞命运。SVZ祖细胞表达适当的BMP特异性I型和II型受体亚基以及选择性BMP配体的转录本,表明存在旁分泌或自分泌发育信号通路(或两者皆有)。这些观察结果表明,BMPs在决定SVZ多能祖细胞或其发育受限程度更高的子代细胞的细胞命运方面具有选择性作用。